A pharmaceutical composition for treating gastritis and a preparation method thereof

Abstract

The present application relates to the field of pharmacy, and in particular to a pharmaceutical composition for treating gastritis and a preparation method thereof. The present application is mainly directed to the degradation of gentamicin procaine granules in a long-term prevention process. The present application prepares granules containing gentamicin by using wet granulation, and then granulates vitamin B12 and procaine together by using dry granulation. Finally, the two parts of the drug-containing granules are mixed, packaged, and then prepared into a dry suspension, so as to ensure the stability of the finished product.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, specifically to a pharmaceutical composition for treating gastritis and its preparation method. Background Technology

[0002] Gentamicin, procaine, and vitamin B12 granules are a compound preparation used to treat chronic, superficial gastritis. Each sachet contains 20mg (20,000 units) of gentamicin sulfate, 0.1g of procaine hydrochloride, and 0.02mg of vitamin B12. Gentamicin sulfate has antibacterial activity against various Gram-negative bacteria, Gram-positive bacteria, and Helicobacter pylori, and its mechanism of action is to inhibit bacterial protein synthesis. Procaine hydrochloride has a local anesthetic effect, and its mechanism of action is to competitively bind firmly to nerve membrane lipoproteins, inhibiting sodium ions and thus nerve fiber conduction. Vitamin B12 is essential for the formation of normal digestive tract epithelial cells. These three components contribute to antibacterial, analgesic, and gastric mucosal repair effects.

[0003] Currently, the commercially available dosage form is granules, which mainly have the following defects: (1) The content stability of gentamicin sulfate is not good. CN202110449797.3 reveals that the commonly used excipient sucrose contains trace amounts of glucose. The open-chain structure of glucose contains aldehyde groups, which are easy to react with the amino groups on the parent ring in the structure of gentamicin, thus leading to the degradation of gentamicin; (2) Procaine hydrochloride is an easily hydrolyzed drug, and most of the currently commercially available preparations adopt wet granulation process, which makes it difficult to avoid the humid and hot environment during the granulation process, thus leading to a decrease in the content of procaine hydrochloride.

[0004] The stability studies of commercially available formulations were conducted, and the results are shown in the table below:

[0005] Changes in the content of gentamicin and procaine are shown in the figure. Figure 1 :

[0006] According to the "Technical Guidelines for Stability Studies of Chemical Drugs (Active Pharmaceutical Ingredients and Preparations)," a 5% difference between the content of a preparation and its initial value indicates a "significant change" in the quality of the preparation. Stability studies on commercially available preparations revealed that the contents of gentamicin and procaine after 24 months were close to or exceeded the 5% limit compared to their initial values, indicating a problem with the stability of the preparations.

[0007] Gentamicin exhibits good heat stability, while procaine is easily hydrolyzed and has a melting point of 61°C. Vitamin B12, however, is unstable when heated. Based on this, this invention develops a novel dosage form and preparation method. Gentamicin, which is heat-stable, is wet-granulated, while procaine and vitamin B12, which are easily hydrolyzed and heat-sensitive, are dry-granulated. Alternatively, the prescribed amounts of raw materials and excipients can be directly dry-granulated, effectively avoiding the defects of the active pharmaceutical ingredient. The resulting formulation exhibits good stability, conforming to the principle of quality by design.

[0008] This invention provides a novel pharmaceutical composition comprising gentamicin, procaine, vitamin B12, a filler, a suspending agent, a lubricant, and a flavoring agent. Gentamicin, procaine, and vitamin B12 are the main drugs. The filler is silicified microcrystalline cellulose and calcium carbonate, wherein calcium carbonate not only serves as a filler but also neutralizes gastric acid. The suspending agent is xanthan gum or hydroxypropyl cellulose. The flavoring agent is any one or more of sodium saccharin and aspartame. The lubricant is any one or more of magnesium stearate or talc. Furthermore, this invention provides a method for preparing this composition, firstly using wet granulation to prepare granules containing gentamicin, then using dry granulation to granulate vitamin B12 and procaine together, and finally mixing the two drug-containing granules and packaging them in separate bags to form a dry suspension, thereby ensuring the stability of the finished product. Summary of the Invention

[0009] This invention provides a pharmaceutical composition for treating gastritis and a method for preparing the same. The pharmaceutical composition has a simple formulation, good stability, and a simple and easy-to-operate preparation method, making it suitable for industrial production.

[0010] This invention uses silicified microcrystalline cellulose and calcium carbonate as fillers. Silicified microcrystalline cellulose is an excipient with good flowability and compressibility, while calcium carbonate not only serves as a filler but also neutralizes stomach acid. The flavoring agent used in this invention does not contain glucose.

[0011] The preparation method of this invention uses stepwise granulation. Wet granulation is used to prepare drug-containing granules containing gentamicin, and then dry granulation is used to prepare drug-containing granules containing procaine and vitamin B12. This avoids a hot and humid environment and conforms to the concept of quality by design.

[0012] The present invention also provides a method for preparing the pharmaceutical composition, wherein all the raw and excipient materials in the prescribed amount are dry granulated, which can also achieve the purpose of the present invention.

[0013] The present invention achieves its objective through the following steps: A pharmaceutical composition for treating gastritis, comprising, by weight percentage, the following components: Gentamicin 2% 10% procaine Vitamin B12 0.002% Filler 55%-70% Suspension agent 5%-30% Flavoring agent 1%-10% Lubricant 0.5%-2% The filler is silicified microcrystalline cellulose or calcium carbonate. The suspending agent is one or more of xanthan gum, hydroxypropyl cellulose, or sodium alginate. The flavoring agent is one or more of sodium saccharin or aspartame. The lubricant is one or more of magnesium stearate or talc.

[0014] The method for preparing the modified pharmaceutical composition provided by the present invention includes the following steps: (1) After premixing gentamicin, suspending agent, filler and flavoring agent in a mixing tank, transfer them to a wet granulator and use purified water to granulate in the wet granulator. (2) After drying the wet granules, they are granulated by passing them through a sieve using a granulator to obtain dry granules containing gentamicin; (3) After mixing procaine, vitamin B12, filler and lubricant in a mixing tank, the mixture is granulated in a dry granulator and the granules are sieved to obtain granules containing procaine and vitamin B12. (4) After mixing the above two portions of medicated dry granules with lubricant in a mixing tank, package them in separate bags.

[0015] The mixing time for steps (1), (3) and (4) of the above method is 5-30 minutes.

[0016] In step (2) of the above method, the drying method is fluidized bed drying or forced-air oven drying, and the drying temperature is 60-80℃.

[0017] In the above method steps (2) and (3), the screen aperture is 0.5-3 mm.

[0018] In the above method, step (2) involves granulation speed of 30-100 rpm.

[0019] The parameters for the above dry granulation are: roller pressure 10-30KN, roller speed 5-10 rpm, and granulation speed 30-100 rpm.

[0020] The present invention also provides a method for preparing the pharmaceutical composition comprising the following steps: After the prescribed amount of raw and auxiliary materials are premixed in a mixing tank, they are transferred to a dry granulation machine. The granules are then sieved and packaged in bags.

[0021] The parameters for the above dry granulation are: roller pressure 10-30KN, roller speed 5-10 rpm, granulation speed 30-100 rpm, and screen aperture 1-3 mm.

[0022] The beneficial results of this invention are that, compared with the prior art, the drug has better stability, the application of excipients in treatment has a synergistic effect, and the preparation process is simple and suitable for industrial production. Attached Figure Description

[0023] Figure 1 Changes in the content of gentamicin and procaine Implementation

[0024] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the methods described are conventional methods, and the active pharmaceutical ingredients can be obtained commercially unless otherwise specified.

[0025] Example 1: Formulation of the pharmaceutical composition

[0026] Preparation process

[0027] Weigh out the prescribed amounts of gentamicin, xanthan gum (or hydroxypropyl cellulose or sodium alginate), calcium carbonate, half an amount of silicified microcrystalline cellulose, and aspartame (or sodium saccharin) into a mixing tank and mix for 5-30 minutes. Then transfer the mixture to a wet granulator and add purified water to granulate.

[0028] The wet particles are transferred to a fluidized bed or a forced-air drying oven and dried until the LOD (rapid moisture content) is less than 1%.

[0029] The dry granules are granulated by passing them through a 1-3 mm sieve to obtain drug-containing dry granules. The granulation speed is 30-100 rpm.

[0030] Weigh out the prescribed amount of procaine, vitamin B12, half a portion of silicified microcrystalline cellulose, and half a portion of magnesium stearate (or talc) and mix them in a mixing tank for 5-30 minutes.

[0031] After mixing, the mixture is granulated using a dry granulator. The granulator parameters are: roller pressure 10-30KN, roller speed 5-10 rpm, and granulation speed 30-100 rpm.

[0032] The granules are passed through a 1-3 mm sieve to obtain granules containing procaine and vitamin B12.

[0033] Mix the two portions of the medicated dry granules with half a portion of the prescription lubricant in a mixing tank for 5-30 minutes, then divide into bags and package.

[0034] According to the requirements of the General Rules for Preparations, Part IV of the 2020 edition of the Chinese Pharmacopoeia, the suspension was tested as follows. The samples of Examples 1-3 were subjected to stability tests under long-term conditions (temperature 25℃±2℃, relative humidity 60%±5%). The test results are shown in the table below.

[0035] Example 1: Detection Results of the Drug Composition

[0036] Example 2: Detection Results of the Drug Composition

[0037] Example 3: Detection Results of the Drug Composition

[0038] Stability tests concluded that the dosages prescribed in Examples 1-3 meet the requirements for drug stability. Compared to existing formulations, the contents of gentamicin and procaine did not decrease under long-term conditions. Other indicators also meet the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0039] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should be considered within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for treating gastritis, characterized in that... The pharmaceutical composition comprises, by weight percentage, the following components: gentamicin 2%, procaine 10%, vitamin B12 0.002%, filler 55%-70%, suspending agent 5%, flavoring agent 1%-10%, and lubricant 0.5%-2%, wherein the filler is silicified microcrystalline cellulose and calcium carbonate, the suspending agent is xanthan gum, the flavoring agent is aspartame, and the lubricant is magnesium stearate; The method for preparing the pharmaceutical composition comprises the following steps: (1) After premixing gentamicin, suspending agent, some filler and flavoring agent in a mixing tank, transfer to a wet granulator and use purified water to granulate in the wet granulator; (2) After the wet granules are dried, they are granulated by passing them through a sieve using a granulator to obtain dry granules containing gentamicin. The sieve aperture is 0.5-3 mm and the granulation speed is 30-100 rpm. (3) After mixing procaine, vitamin B12, the remaining filler and some lubricant in a mixing tank, the mixture is granulated in a dry granulator. The granules are passed through a sieve to obtain dry granules containing procaine and vitamin B12, wherein the sieve aperture is 1-3 mm. (4) After mixing the dry granules obtained in steps (2) and (3) with the remaining lubricant in a mixing tank, they are packaged in separate bags.

2. The pharmaceutical composition according to claim 1, wherein the dosage form of the pharmaceutical composition is a dry suspension.

3. The pharmaceutical composition according to claim 1, characterized in that, The mixing time for steps (1), (3) and (4) is 5-30 minutes.

4. The pharmaceutical composition according to claim 1, characterized in that, Step (2) The drying method is fluidized bed drying or forced-air oven drying, and the drying temperature is 60-80℃.

5. The pharmaceutical composition according to claim 1, characterized in that, The parameters for the dry granulation process are: roller pressure 10-30KN, roller speed 5-10 rpm, and granulation speed 30-100 rpm.

Images